Genetics May Influence Kidney Failure In Blacks

In a case of natural selection with a twist, genetic variants that confer protection against disease in Africa seem to place African Americans half a world away at elevated risk of kidney failure, a new study finds.

U.S. blacks are three times as likely as whites to develop chronic kidney disease. “We think this explains perhaps most of it,” says study coauthor Martin Pollak, a nephrologist and geneticist at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.

The gene in question is called APOL-1, short for apolipoprotein L-1. Among people of African descent, APOL-1 can appear in two variant forms that protect against African sleeping sickness but also increase susceptibility to kidney failure, Pollak and his colleagues report online July 15 in Science.

Each parent provides one gene copy to offspring. The team analyzed blood from more than 1,400 African Americans and found that more than 30 percent carried at least one variant copy of APOL-1. About 10 percent harbored two variant copies.

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Roughly half of the people in the study had kidney disease and half didn’t. The researchers found that those carrying two copies of an APOL-1 gene variant were 10.5 times as likely to have kidney disease marked by loss of blood filtration capacity compared with people who carried the normal APOL-1 gene. The double-copy carriers were 7.3 times more likely to have severe kidney disease marked by high blood pressure that necessitated dialysis or a transplant. People harboring two variant copies were also more prone to such end-stage disease compared with people having one variant copy. While harboring two copies of a variant seemed to increase risk, having one variant and one normal copy did not.